Effect of 2,3-dihydro-1 H-imidazo[1,2-b]pyrazole on the proliferation of mouse leukemic and normal cells in vivo.

Administration of 2,3-dihydro-1 H-imidazo[1,2-b]pyrazole (IMPY; NSC 51143), 250 to 500 mg/kg, in Day 5 L1210 and P388 (ascites) tumor-bearing mice did not consistently prolong the life span of tumor-bearing animals. Flow cytometry and autoradiographic studies showed that, after 12 to 18 hr of a single IMPY injection, both P388 and L1210 tumor cells were synchronized in S phase. In contrast, IMPY inhibited cellular proliferation in both bone marrow and duodenal crypts during the first 24 hr. and a recovery was detectable only after 36 hr, returning to pretherapy values by 72 hr. Preliminary data indicate that this differential response of normal versus tumor cells to IMPY can be exploited to maximize chemotherapeutic efficacy in scheduled chemotherapy with cycle-specific agents.